A study to evaluate the efficacy and safety of fenebrutinib on disability progression and relapse rate in adult participants with RMS. Eligible participants will be randomized in a 1:1 ratio to receive either fenebrutinib or teriflunomide. At the end of the double-blind treatment (DBT) phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension (OLE) phase of the study.

Inclusion Criteria:

• Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening
• A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
• Ability to complete the 9-hole Peg Test (9-HPT) for each hand in < 240 seconds
• Ability to perform the Timed 25-foot Walk Test (T25FWT) in < 150 seconds
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm

OLE Inclusion Criteria:

• Completed the DBT phase of the study (remaining on study treatment; no other disease-modifying therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib
• Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm

Exclusion Criteria:

• Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.0
• Female participants who are pregnant or breastfeeding, or intending to become pregnant
• Male participants who intend to father a child during the study
• A diagnosis of primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
• Any known or suspected active infection at screening, including but not limited to a positive screening tests for hepatitis B (HBV) and hepatitis C (HCV), an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML)
• History of cancer including hematologic malignancy and solid tumors within 10 years of screening
• Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal (GI) disease
• Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
• Hypoproteinemia
• Acute liver disease
• Chronic liver disease unless considered stable for > 6 months
• Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's syndrome
• Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• History of alcohol or other drug abuse within 12 months prior to screening
• History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
• Inability to complete an MRI scan
• Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed)
• Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
• Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period

OLE Exclusion Criteria:

• Chronic liver disease unless considered stable for > 6 months
• Acute liver disease

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Sponsor will also be blinded.